Document Detail

A genomic model for differential hypoxic ventilatory responses.
MedLine Citation:
PMID:  10849650     Owner:  NLM     Status:  MEDLINE    
Inbred mice are routinely used as genetic models in lung biology. Among many phenotypic differences in lung function and structure, C3H/HeJ (C3) and C57BL/6J (B6) inbred mice also demonstrate a significantly different ventilatory pattern during acute hypoxic challenge. The present study rejects the hypothesis that a genomic basis for differential hypoxic ventilatory responses (HVR) is linked to loci which determine differential breathing pattern at baseline, while proposing an alternative genetic model for HVR variation. Twelve BXH recombinant inbred (RI) strains derived from C3 and B6 progenitors were examined to enumerate the genes regulating differential HVR. In each of 134 mice, HVR was assessed using whole-body plethysmography to measure tidal volume (VT) and breathing frequency (f). With respect to f during hypoxia, three distinct and reproducible phenotypes are evident in the BXH RI strain distribution pattern (SDP). The SDP for hypoxic f is consistent with the hypothesis that parental strain differences are regulated by two genes. Cosegregation analysis suggest that the genetic control of f during hypoxia differs from the genes which control differential baseline f. Although the genetic control of VT appears more complex, differences in the minute ventilation (VE) during hypoxia is determined by VT. Therefore, this study suggests that the phenotypic variation in HVR between C3 and B6 parental strains, especially related to f during hypoxia, is regulated by as few as two major genetic determinants.
C G Tankersley
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  475     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2000  
Date Detail:
Created Date:  2000-10-03     Completed Date:  2000-10-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  75-85     Citation Subset:  IM    
Division of Physiology, Johns Hopkins School of Public Health, USA.
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MeSH Terms
Anoxia / genetics*,  physiopathology*
Mice, Inbred C3H
Mice, Inbred C57BL
Models, Genetic*
Recombination, Genetic
Respiration / genetics*
Species Specificity
Tidal Volume / genetics,  physiology
Grant Support

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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